Sodium Carbonate → N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-6-(1H-indazol-5-yl)-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

HRID 476004Notes

Reaction equation

HRID 476004 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:26])[NH:20][C:21]([CH3:25])=[CH:22][C:23]=2[CH3:24])=[O:15])[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[C:37]3[C:41](=[CH:42][CH:43]=2)[NH:40][N:39]=[CH:38]3)O1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O>[CH3:24][C:23]1[CH:22]=[C:21]([CH3:25])[NH:20][C:19](=[O:26])[C:18]=1[CH2:17][NH:16][C:14]([C:4]1[C:5]2[CH:10]=[N:9][N:8]([CH:11]([CH3:13])[CH3:12])[C:6]=2[N:7]=[C:2]([C:35]2[CH:36]=[C:37]3[C:41](=[CH:42][CH:43]=2)[NH:40][N:39]=[CH:38]3)[CH:3]=1)=[O:15]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177504691H-Indazole-5-boronic acid pinacol esterHCID 565974256-Chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide

Product 1

HCID 56598541N-[(4,6-Dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-6-(1H-indazol-5-yl)-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamideYield 48.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

To a 5-mL microwave vial were added 6-chloro-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxamide (70 mg, 0.187 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (59.4 mg, 0.243 mmol), DMSO (1.5 mL) and sodium carbonate (0.281 mL, 0.562 mmol), and the mixture was degassed with nitrogen for 10 min. Next was added bis(triphenylphosphine)palladium(II) chloride (10.51 mg, 0.015 mmol). The contents were sealed and irradiated (microwave) at 140° C. overnight. The mixture was filtered and the residue was washed with DMSO. The crude product in DMSO was purified using reverse-phase HPLC. The TFA salt of the product was neutralized using saturated NaHCO3, filtered, washed with water and dried under high vacuum to give 41 mg (48%) of product. LCMS E-S (M+H)=456.0 1H NMR (400 MHz, DMSO-d6) δ ppm 1.56 (d, J=6.8 Hz, 6H), 2.14 (s, 3H), 2.23 (s, 3H), 4.38-4.53 (m, 2H), 5.27-5.49 (m, 1H), 5.91 (s, 1H), 7.59-7.75 (m, 1H), 8.24 (s, 2H), 8.37 (s, 2H), 8.69 (s, 1H), 8.95-9.09 (m, 1H), 11.49-11.67 (m, 1H), 13.21-13.35 (m, 1H).

Workup

  1. customthe mixture was degassed with nitrogen for 10 min
  2. customThe contents were sealed
  3. customirradiated (microwave) at 140° C. overnight
  4. filtrationThe mixture was filtered
  5. washthe residue was washed with DMSO
  6. customThe crude product in DMSO was purified
  7. filtrationfiltered
  8. washwashed with water
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-a046e721bd2642fe94a40f9edc9e5f37
Source dataset
uspto-grants-2014_01
Patent number
US08637509B2

Reaction notes

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